Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

An emerging role for neutrophil extracellular traps in noninfectious disease

Abstract

The production of neutrophil extracellular traps (NETs) is a process that enables neutrophils to help catch and kill bacteria. However, increasing evidence suggests that this process might also occur in noninfectious, sterile inflammation. In this Review, we describe the role of NETosis in autoimmunity, coagulation, acute injuries and cancer, and discuss NETs as potential therapeutic targets. Furthermore, we consider whether extracellular DNA is always detrimental in sterile inflammation and whether the source is always NETs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Overview of NETosis.
Figure 2: Overview of how NETosis may be involved in noninfectious-disease progression.

Similar content being viewed by others

References

  1. Belaaouaj, A. et al. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat. Med. 4, 615–618 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Takei, H., Araki, A., Watanabe, H., Ichinose, A. & Sendo, F. Rapid killing of human neutrophils by the potent activator phorbol 12-myristate 13-acetate (PMA) accompanied by changes different from typical apoptosis or necrosis. J. Leukoc. Biol. 59, 229–240 (1996).

    Article  CAS  PubMed  Google Scholar 

  3. Brinkmann, V. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532–1535 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Metzler, K.D., Goosmann, C., Lubojemska, A., Zychlinsky, A. & Papayannopoulos, V. A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis. Cell Rep. 8, 883–896 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Papayannopoulos, V., Metzler, K.D., Hakkim, A. & Zychlinsky, A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J. Cell Biol. 191, 677–691 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yipp, B.G. & Kubes, P. NETosis: how vital is it? Blood 122, 2784–2794 (2013).

    Article  CAS  PubMed  Google Scholar 

  7. Clark, S.R. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat. Med. 13, 463–469 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Pilsczek, F.H. et al. A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J. Immunol. 185, 7413–7425 (2010).

    Article  CAS  PubMed  Google Scholar 

  9. Yipp, B.G. et al. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat. Med. 18, 1386–1393 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rochael, N.C. et al. Classical ROS-dependent and early/rapid ROS-independent release of neutrophil extracellular traps triggered by Leishmania parasites. Sci. Rep. 5, 18302 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Slaba, I. et al. Imaging the dynamic platelet-neutrophil response in sterile liver injury and repair in mice. Hepatology 62, 1593–1605 (2015).

    Article  CAS  PubMed  Google Scholar 

  12. Yousefi, S., Mihalache, C., Kozlowski, E., Schmid, I. & Simon, H.U. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ. 16, 1438–1444 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Lood, C. et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat. Med. 22, 146–153 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kolaczkowska, E. et al. Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature. Nat. Commun. 6, 6673 (2015).

    Article  CAS  PubMed  Google Scholar 

  15. Branzk, N. et al. Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat. Immunol. 15, 1017–1025 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Schauer, C. et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat. Med. 20, 511–517 (2014).

    Article  CAS  PubMed  Google Scholar 

  17. Kolaczkowska, E. & Kubes, P. Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13, 159–175 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Fournier, B.M. & Parkos, C.A. The role of neutrophils during intestinal inflammation. Mucosal Immunol. 5, 354–366 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. Soehnlein, O. & Lindbom, L. Phagocyte partnership during the onset and resolution of inflammation. Nat. Rev. Immunol. 10, 427–439 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Hurst, S.M. et al. Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity 14, 705–714 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Tsuda, Y. et al. Three different neutrophil subsets exhibited in mice with different susceptibilities to infection by methicillin-resistant Staphylococcus aureus. Immunity 21, 215–226 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Zhang, D. et al. Neutrophil ageing is regulated by the microbiome. Nature 525, 528–532 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gupta, S. & Kaplan, M.J. The role of neutrophils and NETosis in autoimmune and renal diseases. Nat. Rev. Nephrol. 12, 402–413 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Denny, M.F. et al. A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs. J. Immunol. 184, 3284–3297 (2010).

    Article  CAS  PubMed  Google Scholar 

  25. Garcia-Romo, G.S. et al. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci. Transl. Med. 3, 73ra20 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Carmona-Rivera, C., Zhao, W., Yalavarthi, S. & Kaplan, M.J. Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2. Ann. Rheum. Dis. 74, 1417–1424 (2015).

    Article  CAS  PubMed  Google Scholar 

  27. Villanueva, E. et al. Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus. J. Immunol. 187, 538–552 (2011).

    Article  CAS  PubMed  Google Scholar 

  28. Hakkim, A. et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc. Natl. Acad. Sci. USA 107, 9813–9818 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Campbell, A.M., Kashgarian, M. & Shlomchik, M.J. NADPH oxidase inhibits the pathogenesis of systemic lupus erythematosus. Sci. Transl. Med. 4, 157ra141 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Winkelstein, J.A. et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine 79, 155–169 (2000).

    Article  CAS  PubMed  Google Scholar 

  31. Sur Chowdhury, C. et al. Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility. Arthritis Res. Ther. 16, R122 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Khandpur, R. et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci. Transl. Med. 5, 178ra40 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang, W., Jian, Z., Guo, J. & Ning, X. Increased levels of serum myeloperoxidase in patients with active rheumatoid arthritis. Life Sci. 117, 19–23 (2014).

    Article  CAS  PubMed  Google Scholar 

  34. Christensen, A.D., Haase, C., Cook, A.D. & Hamilton, J.A. K/BxN serum-transfer arthritis as a model for human inflammatory arthritis. Front. Immunol. 7, 213 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Maicas, N. et al. Deficiency of Nrf2 accelerates the effector phase of arthritis and aggravates joint disease. Antioxid. Redox Signal. 15, 889–901 (2011).

    Article  CAS  PubMed  Google Scholar 

  36. Huang, X. et al. Neutrophils regulate humoral autoimmunity by restricting nterferon-γ production via the generation of reactive oxygen species. Cell Rep. 12, 1120–1132 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lee, H.T. et al. The pathogenesis of systemic lupus erythematosus—From the viewpoint of oxidative stress and mitochondrial dysfunction. Mitochondrion 30, 1–7 (2016).

    Article  CAS  PubMed  Google Scholar 

  38. Rohrbach, A.S., Hemmers, S., Arandjelovic, S., Corr, M. & Mowen, K.A. PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis. Arthritis Res. Ther. 14, R104 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Seri, Y. et al. Peptidylarginine deiminase type 4 deficiency reduced arthritis severity in a glucose-6-phosphate isomerase-induced arthritis model. Sci. Rep. 5, 13041 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Willis, V.C. et al. N-α-benzoyl-N5-(2-chloro-1-iminoethyl)-l-ornithine amide, a protein arginine deiminase inhibitor, reduces the severity of murine collagen-induced arthritis. J. Immunol. 186, 4396–4404 (2011).

    Article  CAS  PubMed  Google Scholar 

  41. Wang, Y. et al. Increased neutrophil elastase and proteinase 3 and augmented NETosis are closely associated with β-cell autoimmunity in patients with type 1 diabetes. Diabetes 63, 4239–4248 (2014).

    Article  CAS  PubMed  Google Scholar 

  42. Rodríguez-Espinosa, O., Rojas-Espinosa, O., Moreno-Altamirano, M.M., López-Villegas, E.O. & Sánchez-García, F.J. Metabolic requirements for neutrophil extracellular traps formation. Immunology 145, 213–224 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wong, S.L. et al. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat. Med. 21, 815–819 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Joshi, M.B. et al. High glucose modulates IL-6 mediated immune homeostasis through impeding neutrophil extracellular trap formation. FEBS Lett. 587, 2241–2246 (2013).

    Article  CAS  PubMed  Google Scholar 

  45. Papayannopoulos, V. Sweet NETs, bitter wounds. Immunity 43, 223–225 (2015).

    Article  CAS  PubMed  Google Scholar 

  46. Fadini, G.P. et al. NETosis delays diabetic wound healing in mice and humans. Diabetes 65, 1061–1071 (2016).

    Article  CAS  PubMed  Google Scholar 

  47. Kallenberg, C.G. Key advances in the clinical approach to ANCA-associated vasculitis. Nat. Rev. Rheumatol. 10, 484–493 (2014).

    Article  CAS  PubMed  Google Scholar 

  48. Kessenbrock, K. et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat. Med. 15, 623–625 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Pendergraft, W.F. III et al. Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human autoantigen proteinase-3. Nat. Med. 10, 72–79 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Thieblemont, N., Wright, H.L., Edwards, S.W. & Witko-Sarsat, V. Human neutrophils in auto-immunity. Semin. Immunol. 28, 159–173 (2016).

    Article  CAS  PubMed  Google Scholar 

  51. Harper, L., Cockwell, P., Adu, D. & Savage, C.O. Neutrophil priming and apoptosis in anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Kidney Int. 59, 1729–1738 (2001).

    Article  CAS  PubMed  Google Scholar 

  52. Söderberg, D. et al. Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission. Rheumatology (Oxford) 54, 2085–2094 (2015).

    Article  Google Scholar 

  53. Rao, A.N., Kazzaz, N.M. & Knight, J.S. Do neutrophil extracellular traps contribute to the heightened risk of thrombosis in inflammatory diseases? World J. Cardiol. 7, 829–842 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Imamoto, T. et al. Possible linkage between microscopic polyangiitis and thrombosis via neutrophil extracellular traps. Clin. Exp. Rheumatol. 32, 149–150 (2014).

    PubMed  Google Scholar 

  55. Stakos, D.A. et al. Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction. Eur. Heart J. 36, 1405–1414 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kambas, K. et al. Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease. Ann. Rheum. Dis. 73, 1854–1863 (2014).

    Article  CAS  PubMed  Google Scholar 

  57. Semeraro, F. et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood 118, 1952–1961 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Massberg, S. et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat. Med. 16, 887–896 (2010).

    Article  CAS  PubMed  Google Scholar 

  59. Martinod, K. et al. Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis. J. Thromb. Haemost. 14, 551–558 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rangé, H. et al. Periodontal bacteria in human carotid atherothrombosis as a potential trigger for neutrophil activation. Atherosclerosis 236, 448–455 (2014).

    Article  CAS  PubMed  Google Scholar 

  61. Warnatsch, A., Ioannou, M., Wang, Q. & Papayannopoulos, V. Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349, 316–320 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Swirski, F.K. & Nahrendorf, M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 339, 161–166 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Nahrendorf, M. & Swirski, F.K. Immunology. Neutrophil-macrophage communication in inflammation and atherosclerosis. Science 349, 237–238 (2015).

    Article  CAS  PubMed  Google Scholar 

  64. Demers, M. & Wagner, D.D. NETosis: a new factor in tumor progression and cancer-associated thrombosis. Semin. Thromb. Hemost. 40, 277–283 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sionov, R.V., Fridlender, Z.G. & Granot, Z. The multifaceted roles neutrophils play in the tumor microenvironment. Cancer Microenviron. 8, 125–158 (2015).

    Article  CAS  PubMed  Google Scholar 

  66. Jenne, C.N. & Kubes, P. Gastrointestinal cancer: Neutrophils and cancer: guilt by association. Nat. Rev. Gastroenterol. Hepatol. 13, 381–382 (2016).

    Article  CAS  PubMed  Google Scholar 

  67. Guglietta, S. et al. Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis. Nat. Commun. 7, 11037 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Levi, M. Management of cancer-associated disseminated intravascular coagulation. Thromb. Res. 140 (Suppl. 1), S66–S70 (2016).

    Article  CAS  PubMed  Google Scholar 

  69. Ho-Tin-Noé, B. et al. Innate immune cells induce hemorrhage in tumors during thrombocytopenia. Am. J. Pathol. 175, 1699–1708 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Breitbach, C.J. et al. Targeting tumor vasculature with an oncolytic virus. Mol. Ther. 19, 886–894 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Cedervall, J. et al. Neutrophil extracellular traps accumulate in peripheral blood vessels and compromise organ function in tumor-bearing animals. Cancer Res. 75, 2653–2662 (2015).

    Article  CAS  PubMed  Google Scholar 

  72. Cools-Lartigue, J. et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J. Clin. Invest. 123, 3446–3458 (2013).

    Article  CAS  PubMed Central  Google Scholar 

  73. Hampson, P. et al. Neutrophil dysfunction, immature granulocytes, and cell-free DNA are early biomarkers of sepsis in burn-injured patients: a prospective observational cohort study. Ann. Surg. http://dx.doi.org/10.1097/SLA.0000000000001807 (2016).

  74. Allam, R., Kumar, S.V., Darisipudi, M.N. & Anders, H.J. Extracellular histones in tissue injury and inflammation. J. Mol. Med. (Berl.) 92, 465–472 (2014).

    Article  CAS  Google Scholar 

  75. Malachowa, N., Kobayashi, S.D., Freedman, B., Dorward, D.W. & DeLeo, F.R. Staphylococcus aureus leukotoxin GH promotes formation of neutrophil extracellular traps. J. Immunol. 191, 6022–6029 (2013).

    Article  CAS  PubMed  Google Scholar 

  76. Wang, J. & Kubes, P. A reservoir of mature cavity macrophages that can rapidly invade visceral organs to affect tissue repair. Cell 165, 668–678 (2016).

    Article  CAS  PubMed  Google Scholar 

  77. Garcia, R.J. et al. Attention deficit and hyperactivity disorder scores are elevated and respond to N-acetylcysteine treatment in patients with systemic lupus erythematosus. Arthritis Rheum. 65, 1313–1318 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lai, Z.W. et al. N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 64, 2937–2946 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Van Avondt, K., van der Linden, M., Naccache, P.H., Egan, D.A. & Meyaard, L. Signal inhibitory receptor on leukocytes-1 limits the formation of neutrophil extracellular traps, but preserves intracellular bacterial killing. J. Immunol. 196, 3686–3694 (2016).

    Article  CAS  PubMed  Google Scholar 

  80. Van Avondt, K., Fritsch-Stork, R., Derksen, R.H. & Meyaard, L. Ligation of signal inhibitory receptor on leukocytes-1 suppresses the release of neutrophil extracellular traps in systemic lupus erythematosus. PLoS One 8, e78459 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Martinod, K. et al. PAD4-deficiency does not affect bacteremia in polymicrobial sepsis and ameliorates endotoxemic shock. Blood 125, 1948–1956 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hemmers, S., Teijaro, J.R., Arandjelovic, S. & Mowen, K.A. PAD4-mediated neutrophil extracellular trap formation is not required for immunity against influenza infection. PLoS One 6, e22043 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Knight, J.S. et al. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice. Ann. Rheum. Dis. 74, 2199–2206 (2015).

    Article  CAS  PubMed  Google Scholar 

  84. Knight, J.S. et al. Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ. Res. 114, 947–956 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Lewis, H.D. et al. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat. Chem. Biol. 11, 189–191 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zheng, W. et al. PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis. J. Pharmacol. Exp. Ther. 353, 288–298 (2015).

    Article  CAS  PubMed  Google Scholar 

  87. Sayah, D.M. et al. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am. J. Respir. Crit. Care Med. 191, 455–463 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Macanovic, M. et al. The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone. Clin. Exp. Immunol. 106, 243–252 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Davis, J.C. Jr. et al. Recombinant human Dnase I (rhDNase) in patients with lupus nephritis. Lupus 8, 68–76 (1999).

    Article  PubMed  Google Scholar 

  90. Domingo-Gonzalez, R. et al. Inhibition of neutrophil extracellular trap formation after stem cell transplant by prostaglandin E2. Am. J. Respir. Crit. Care Med. 193, 186–197 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Shishikura, K. et al. Prostaglandin E2 inhibits neutrophil extracellular trap formation through production of cyclic AMP. Br. J. Pharmacol. 173, 319–331 (2016).

    Article  CAS  PubMed  Google Scholar 

  92. Barnado, A., Crofford, L.J. & Oates, J.C. At the Bedside: Neutrophil extracellular traps (NETs) as targets for biomarkers and therapies in autoimmune diseases. J. Leukoc. Biol. 99, 265–278 (2016).

    Article  CAS  PubMed  Google Scholar 

  93. Rai, R., Chauhan, S.K., Singh, V.V., Rai, M. & Rai, G. RNA-seq analysis reveals unique transcriptome signatures in systemic lupus erythematosus patients with distinct autoantibody specificities. PLoS One 11, e0166312 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Chang, H.H., Dwivedi, N., Nicholas, A.P. & Ho, I.C. The W620 polymorphism in PTPN22 disrupts its interaction with peptidylarginine deiminase type 4 and enhances citrullination and NETosis. Arthritis Rheumatol. 67, 2323–2334 (2015).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank C. Deppermann for proofreading the manuscript. Work in the authors' laboratory is supported by grants from the Canadian Institutes of Health Research, Alberta Innovates Health Solutions, the Heart and Stroke Foundation of Canada and the Canada Research Chairs program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paul Kubes.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jorch, S., Kubes, P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat Med 23, 279–287 (2017). https://doi.org/10.1038/nm.4294

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.4294

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing